The Vascular Endothelial Cell Antigen System

J, Cerilli; Brasile, Lauren; Galouzis, Tom; Lempert, Neil; Clarke, John

doi:10.1097/00007890-198503000-00016

Cited by 101 publications

(36 citation statements)

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“…Lymphocytotoxic antibodies (18)(19)(20)(21) and possibly reticuloendothelial-specific (22) antibodies have also been shown to have similar effects. The target of destruction is the kidney microvasculature, which is ruined and plugged with thrombi so quickly that the descriptive term hyperacute rejection has been applied.…”

Section: Discussionmentioning

confidence: 99%

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

et al. 1992

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Twenty-six adult patients with preformed IgG donor lymphocytotoxic antibodies received primary liver allografts under FK 506 immunosuppression. The effect of the crossmatch-positive state on early graft function and on the immunopathological and histo-pathological findings was compared with that of 52 crossmatch-negative control recipients. The presensitized (Crossmatch-positive) patients had prolongation of early graft dysfunction, underwent more clinically indicated biopsies and had a higher incidence of cellular rejection, both overall (p < 0.05) and within 10 days of transplantation (p < 0.01). They also had a higher incidence of graft failure in the first 180 days (p < 0.01). Hyperacute rejection with necrotizing or neutrophilic arteritis was not seen in the crossmatchpositive grafts. However, histological findings associated with presensitization included platelet margination in central veins and sinusoids in biopsy specimens 60 to 90 min after graft revascularization. Later biopsy specimens had neutrophilic portal venulitis followed by cholangiolar proliferation, acute cholangiolitis and centrilobular hepatocyte swelling that mimicked preservation injury, endothelial activation of arteries with medial changes and relapsing episodes of acute cellular rejection. These clinicopathological observations suggest that lymphocytotoxic antibodies can have a deleterious effect on liver allograft function and survival, even if they do not precipitate immediate or hyperacute rejection. (Hepatology 1992;16:671-681.) Although the liver is known to be more resistant than other solid organs to injury from preformed graft antibodies in the recipient (1-3), this privileged state is not absolute (4,5). Identification of the consequences of humoral antibody states on the liver has been hampered by the lack of distinctive pathological findings in many cases in which humoral rejection was suspected but was not proved. Consequently, in this study of liver recipients with preformed donor lymphocytotoxic antibodies, we have attempted to determine whether a unique, pathologically identifiable form of graft injury could be recognized and whether pathophysiological mechanisms of liver allograft injury could be deduced. A similar study on the pathological nature of ABO-mismatched livers in which the graft antibodies were isoagglutinins was published recently (6). MATERIALS AND METHODS Patient SelectionDuring the 11-mo period between November 31, 1989, and September 9, 1990, 243 adult patients ( > 16 yr) were given primary liver allografts under FK 506 and low-dose steroid therapy. The sera of 26 (11%) contained donor lymphocytotoxic antibodies. The crossmatchnegative control patients (n = 52) were those treated just before and after the crossmatchpositive cases. Most of these same cases were part of a recent clinical report (5). There were no statistically significant differences between the two cohorts with respect to age, United Network of Organ Sharing urgency of need status, original disease, donor demographic data or...

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Section: Discussionmentioning

confidence: 99%

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

et al. 1992

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“…In transplantation, the presence of alloantibodies to non-HLA antigens -mostly being reported associated with endothelial cells and monocytes and not detectable on B and T cells -has been previously reported in HLA-identical kidney transplants, indicating that non-HLA antigens might also be targets for transplant rejection (10,11). Studies of HLA-identical living related donor allografts have shown that the presence of endothelial-monocyte reactive, cytotoxic IgM antibodies correlated with rejection, graft loss and poor allograft outcome.…”

Section: Introductionmentioning

confidence: 94%

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Bas‐Bernardet

Hourmant

Coupel

et al. 2003

American Journal of Transplantation

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The vascular endothelium of transplanted organs represents an important target for allograft-directed immune responses. Although HLA antigens expressed on graft endothelial cells (EC) can become targets of the host immune response, the role of other, non-HLA-encoded EC antigens has been proposed but is still unclear. The aim of this study was to investigate the presence of and to characterize anti-EC antibodies (AECA) in 57 kidney transplant recipients according to their HLAimmunization status. Flow cytometry in pretransplant sera was used to detect AECA reactive with surface antigens on ABO and HLA-typed primary cultures of arterial ECs, stimulated or not with tumor necrosis factor-a (TNFa) or interferon-g (IFNg). FACS analysis revealed the presence of AECA in 47% of HLA-sensitized (PRA = 10%: mostly IgG) vs. 16.0% in nonsensitized patients (PRA < 10%) (p < 0.02). No significant correlation was found between the presence of AECA and acute rejection occurrence and graft outcome. Non-HLA reactive AECA are directed against TNFa-and IFNg-inducible membrane molecule(s), and react with two predominant antigens of~35 kDa and~50 kDa expressed on ECs but not on B cells. Binding of AECA decreases in vitro EC viability by 50-60% by promoting EC apoptosis, as demonstrated by DNA fragmentation assays.

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“…It represents an important target for allograftdirected immune responses (1). By expressing both class I and class II human leukocyte antigens (HLA), activated graft endothelium may become a target for anti-HLA antibodies leading to acute or chronic allograft rejection (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection

Han

Lü²,

Jin³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: Endothelial cell antigens are important targets in acute rejection (AR). Our goal was to measure the serum concentrations of pre-transplant antiendothelial cell antibody (AECA) in panel reactive antibody (PRA) negative recipients and its impact on AR within 6 months following renal transplantation. Methods: We retrospectively examined pre-transplant sera from 392 patients using cellular enzyme linked immunosorbent assay (ELISA) with substrate from a permanent endothelial cell line EAhy926. Equal volumes of serum from 40 healthy volunteers were mixed and used as the negative control. Results: The positive rate of AECA was 15.8%. There were no significant differences with respect to age, gender, original disease, dialysis history, immune suppressive regimen, cytomegalovirus (CMV) antigen positive rate, complement dependent cytotoxicity (CDC) level and soluble CD30 (sCD30) levels between the AECA positive group and AECA negative group. AR rate in the AECA positive group was higher than that in the AECA negative group (35.5% vs. 22.4%, ps0.023). The AECA positive patients had significantly higher rates of acute grade II T-cell mediated rejection (TMR) and acute antibody mediated rejection (AMR) compared with AECA negative patients. The concentrations of sCD30, and AECA were independent risk factors for AR within 6 months; the odds ratios were 7.005 and 2.469, respectively. Conclusions: Positive AECA was an independent risk factor for AR and appeared to correlate with relatively severe rejection subtypes. Clin Chem Lab Med 2009;47:1265-9.

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The Vascular Endothelial Cell Antigen System

Cited by 101 publications

References 0 publications

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

A clinicopathological study of human liver allograft recipients harboring preformed IgG lymphocytotoxic antibodies

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection

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